Why haven’t we cured inflammatory bowel disease?

David Rubin, MD, Section Chief of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine (left) and Russell Cohen, MD, Director of the Inflammatory Bowel Disease Center at UChicago Medicine (right) (Photo: Jean Lachat)

David Rubin, MD, recently hosted an information session for patients titled, “Why haven’t we cured Crohn’s disease and ulcerative colitis?” Rubin, who is Section Chief of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, co-hosted the session with Russell Cohen, MD, Director of the Inflammatory Bowel Disease Center at UChicago Medicine. He said the idea for their session came from a similar question asked by a patient years ago.

“I gave a lecture to patients about managing inflammatory bowel disease. Someone came up to me afterwards and said, ‘Dr. Rubin, that was a great lecture, but you never once mentioned a cure. We want to hear about cures,’” he said. “That really reflected on me in a way that was profound. I was so focused on what we do day-to-day, that I was losing track of the bigger picture.”

We spoke to Rubin recently about what it would mean to “cure” Crohn’s disease and ulcerative colitis, collectively known as inflammatory bowel disease or IBD. He said the key to getting there is to help each patient understand that IBD is really a range of diseases that need a range of specific, personalized treatments to control symptoms to the point that one could begin to think of a cure. What follows is an edited version of that conversation.

UChicagoMed: What do you tell patients now when they ask why there isn’t a cure for IBD?

David Rubin, MD: There are different ways to approach this question, but one of them is to remind them that we don’t really cure any chronic human diseases, except for infections. Most of these problems are not cured because they’re so complicated.

We’ve labeled Crohn’s disease and ulcerative colitis as two diseases, but we’ve come to realize that they are maybe 50 to 100 different diseases that are all overlapping. The body can express itself in very specific and limited ways, so anything that results in overactive inflammation or some imbalanced immune response can look like one of these diseases. So the first part is that when you talk about a “cure,” you should really be talking about “cures,” and when you talk about cures you have to define what all the different disease subsets are.

The second piece to this is that even when we can isolate a very specific, similar type of condition, we’ve come to realize that there’s still a very complex interplay between genetics and the environment that leads to it. That makes it very hard then to figure out how to treat it.

Since the disease can be one of many different, complex things, treatment may also be a very complex set of things. Do you think that’s harder for a patient to understand, that the cure isn’t just one thing?

It’s frustrating for people. They want to believe they can be cured and they want to minimize the therapy exposures, and we understand that. I don’t think it’s hard for a patient to understand once you bother to explain it, but I think too often physicians don’t explain it. We need to emphasize to people that everyone who has IBD is different, and people have different forms and shapes and flavors of it based on all these different factors. Once a patient understands that “my IBD is my IBD,” then they should understand a little more that the way they’re treated, the way they’re going to respond, and what we can do for long-term health may be different and needs to be customized.

We don’t want to say to people, “Here’s why we haven’t cured IBD, good luck.” We want to say, “Here’s why we haven’t cured IBD, but in fact we have some options that provide the closest thing to a cure that you may not be aware of.” We have changed the natural history of these diseases for most patients now.

What are some of the most promising new developments for treating IBD?

The first thing that’s most promising is not actually a new set of drugs, but a change of strategy with existing therapies. We have learned how to use them properly, which means at the right time in the right patients, to optimize them and achieve objective endpoints through a strategy called “treat to target.” You identify a target for a patient, which may be diminished inflammation or a healed mucosa, and you adjust the treatment sequentially until you hit that target. This way we can achieve much better control in most people.

The second part is the emergence of additional targeted therapies that are either gut-specific, meaning they only target the immune system of the bowel, which is nice, or target different components of the immune system that we haven’t targeted before in IBD.

The other major thing that’s going to change in the world of IBD in the next two years is the entry into the US market of biosimilar therapies. These are drugs that are biologically similar to the existing biologic therapies that we have, so the closest comparison is to say it’s like a generic biologic. It’s going to drive the price down for a lot of these therapies, and when the price comes down, we think that more payers and more people will be willing to use them. We know these therapies provide the best control, so hopefully we’re going to lower the bar on getting people on good therapies that will change what they do.

Further on the horizon, what kind of research is taking place for IBD?

One of the biggest areas of research right now is the microbiome, and understanding the environment of the organisms that live in the gut. So if you can understand a little bit more about what’s going on with the organisms that are living in the colon, and you combine that with different genetic factors that are related to the disease, we’re going to start finding patterns where there’s a genetic susceptibility to the disease. When that’s combined with a specific group of organisms or an ecosystem in the gut for some reason exploits that genetic susceptibility, it leads to this uncontrolled response.

You might imagine a time in the future when we get a little better handle on this, that what we will be able to target the host by modifying the immune response with some of the therapies we have now, or maybe some future therapies. Then we’ll also target the ecosystem in the gut by manipulating the microbiome in some way to provide better control of what’s going on by turning off the abnormal or immune response.

What do you think is a reasonable expectation to tell patients who ask you if they can be “cured”?

Patients should be reassured that we’re looking for cures. We haven’t given up. There are some people on the internet who believe in this conspiracy of Big Pharma. The reality is that we’ve never spent more, invested more, or had smarter people working on the cause of IBD than we have now. That’s an important message.

The second part is that while we’re looking for the cure, we shouldn’t ignore the fact that you should still have your condition treated and under control. We can do that now better than ever before, and that those who continue to believe in magical thinking that unproven strategies are somehow going to work for them, that if they just change their diet they’re going to get better, are unfortunately in denial and also likely to suffer consequences of that strategy.

But by adopting a treat to target strategy of looking for objective markers of disease control, if a patient doesn’t want to use the therapies that are being recommended, any strategy can be held to the same standard. So a physician can work with a patient and say, “Fine. If you really believe that diet is what triggered this, and you want to try to modify your diet to treat it, I’m willing to let you do that. I’ll give you six weeks, which is enough time to see a response, and we’re going to repeat your labs and see if you’ve gotten better.” After that, when you see if they are or they aren’t getting better, then we’ll continue to move forward together. I think that appreciation has been a huge advance in our field.